Antidiabetes and antioxidant potential of Schiff bases derived from 2-naphthaldehye and substituted aromatic amines: Synthesis, crystal structure, Hirshfeld surface analysis, computational, and invitro studies.

Three Schiff bases were synthesised by the condensation reaction between 2-napthaldehyde and aromatic amines to afford (E)-N-mesityl-1-(naphthalen-2-yl)methanimine (L1), (E)-N-(2,6-dimethylphenyl)-1-(naphthalen-2-yl)methanimine (L2) and (E)-N-(2,6-diisopropylphenyl)-1-(naphthalen-2-yl)methanimine (L3). The synthesised compounds were characterised using UV-visible, NMR (13C & 1H), and Fourier transform infrared spectroscopic methods while their purity was ascertained by elemental analysis. Structural analysis revealed that the naphthalene ring is almost coplanar with the imine functional group as evident by C1-C10-C11-N1 torsion angles of 176.4(2)° and 179.4(1)° in L2 and L3, respectively. Of all the various intermolecular contacts, H⋯H interactions contributed mostly towards the Hirshfeld surfaces of both L2 (58.7 %) and L3 (69.7 %). Quantum chemical descriptors of L1 - L3 were determined using Density Functional Theory (DFT) and the results obtained showed that the energy band gap (ΔE) for L1, L2 and L3 are 3.872, 4.023 and 4.004 eV respectively. The antidiabetic potential of the three compounds were studied using α-amylase and α-glucosidase assay. Compound L1 showed very promising antidiabetic activities with IC50 values of 58.85 µg/mL and 57.60 µg/mL while the reference drug (Acarbose) had 405.84 µg/mL and 35.69 µg/mL for α-amylase and α-glucosidase respectively. In-silico studies showed that L1 docking score as well as binding energies are higher than that of acarbose, which are recognized inhibitors of α-amylase together with α-glucosidase. Further insight from the RMSF, RMSD and RoG analysis predicted that, throughout the simulation L1 showcased evident influence on the structural stability of α-amylase. The antioxidant potential of the compounds was carried out using nitric oxide (NO), ferric reducing ability power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. The compounds exhibited good to fairly antioxidant properties with L1 as well as L3 having IC50 values of 70.91 and 91.21 µg/mL respectively for NO scavenging activities assay, which comparatively outshined acarbose (reference drug) with IC50 value of 109.95 µg/mL. Pharmacology and pharmacokinetics approximations of L1 - L3 showed minimal violation of Lipinski's Ro5 and this projects them to be less toxic and orally bioavailable as potential templates for the design of therapeutics with antioxidant and antidiabetic activities.

Ni2+ and Cu2+ complexes of N-(2,6-dichlorophenyl)-N-mesityl formamidine dithiocarbamate structural and functional properties as CYP3A4 potential substrates.

Metal compounds continued to attract diverse applications due to their malleability in several capacities. In this study, we present our findings on the crystal structures and functional properties of Ni2+ and Cu2+ complexes of N'-(2,6-dichlorophenyl)-N-mesitylformamidine dithiocarbamate (L) comprising [Ni-(L)2] (1) and [Cu-(L)2] (2) with a four-coordinate metal center. We established the two complex structures through 1H and 13C nuclear magnetic resonance (NMR), elemental, and single-crystal X-ray analysis. The analyses showed that the two complexes are isomorphous, having P21/c as a space group and a unit-cell similarity index (π) of 0.002. The two complexes conform to a distorted square planar geometry around the metal centers. The calculated and experimental data, including bond lengths, angles, and NMR values, are similar. Hirshfeld surface analysis revealed the variational contribution of the different types of intermolecular contacts driven by the crystal lattice of the two solvated complexes. Our knowledge of the potential biological implication of these structures enabled us to probe the compounds as prospective CYP3A4 inhibitors. This approach mimics current trends in pharmaceutical design and biomedicine by incorporating potentially active molecules into various media to predict their biological efficacies. The simulations show appreciable binding of compounds 1 and 2 to CYP3A4 with average interaction energies of -97 and -87 kcal/mol, respectively. The protein attains at least five conformational states in the three studied models using a Gaussian Mixture Model-based clustering and free energy prediction. Electric field analysis shows the crucial residues to substrate binding at the active site, enabling CYP3A4 structure to function prediction. The predicted inhibition with these Ni2+ and Cu2+ complexes indicates that CYP3A4 overexpression in a diseased state like cancer would reduce, thereby increasing the chemotherapeutic compounds' shelf-lives for adsorption. This multidimensional study addresses various aspects of molecular metal electronics, including their application as substrate-mimicking inhibitors. The outcome would enable further research on bio-metal compounds of critical potential.

The link between relative stability constant of DNA- and BSA-chromenopyrimidine complexes and cytotoxicity towards human breast cancer cells (MCF-7).

In this study, we synthesized and characterized ten chromenopyrimidine derivatives using analytical and spectroscopic methods. Studies on DNA and albumin binding affinity, as well as cytotoxicity tests on human breast cancer (MCF-7) cells, of the chromenopyrimidines, were conducted. The natural logarithm of the relative stability constant of DNA- and BSA-chromenopyrimidine complexes [ln(KDNA/KBSA)] was used as a criterion for selecting compounds for cytotoxicity studies. We found that ln(KDNA/KBSA) was inversely related to IC50 values of the compounds in MCF-7 cells. The antiproliferative effects of the compounds were found to induce apoptosis in MCF-7 cells, which is a desired mechanism of cell death. Correlations between the DNA and albumin binding affinities of chromenopyrimidines were established. We propose that this relationship approach can, for a given set of compounds, assist in predicting the cytotoxicity of potential drug candidates towards MCF-7 cells based on their experimentally determined CT-DNA and BSA binding affinities.

Silver(I) pyridinyl complexes with benzothiazole, thiophene, and furan moieties: DNA/protein-binding, antibacterial, antioxidant, and anticancer studies.

We have synthesized and characterized nine Ag(I) complexes of Schiff bases containing thiophene, furan, and pyridine moieties for in vitro antibacterial, antioxidant, anticancer activities, and DNA/bovine serum albumin (BSA) binding studies. Based on the analytical and spectral analyses, a linear geometry was proposed for all the Ag(I) complexes, except for one (with the furan moiety), which formed a distorted T-shaped geometry. UV-vis absorption studies on the interactions of calf thymus-DNA (CT-DNA) with the nine Ag(I) complexes pointed to an intercalative binding mode. With a binding constant Kb of 3.75 × 105 M-1 , the complex bearing a benzothiazole moiety (1) interacted stronger with CT-DNA than the rest of the complexes. Fluorescence spectroscopic data revealed that the complexes had a modest binding affinity for BSA through static quenching. The complexes displayed good antioxidant properties, especially those with a benzothiazole moiety. Notable antibacterial activities against methicillin-resistant Staphylococcus aureus, Staphylococcus aureus, Salmonella typhimurium, Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae were observed for complexes with the furan and thiophene moieties. The in vitro anticancer studies of selected complexes against three cancer cell lines showed that the complexes were more effective against the inhibition of the growth of cervical cancer cells relative to cisplatin.

A study of structure-activity relationship and anion-controlled quinolinyl Ag(I) complexes as antimicrobial and antioxidant agents as well as their interaction with macromolecules.

In this communication, we feature the synthesis and in-depth characterization of a series of silver(I) complexes obtained from the complexation of quinolin-4-yl Schiff base ligands ((E)-2-((quinolin-4-ylmethylene)amino)phenol La, 2-(quinolin-4-yl)benzo[d]thiazole Lb, (E)-N-(2-fluorophenyl)-1-(quinolin-4-yl)methanimine Lc, (E)-N-(4-chlorophenyl)-1-(quinolin-4-yl)methanimine Ld, (E)-1-(quinolin-4-yl)-N-(p-tolyl)methanimine Le, (E)-1-(quinolin-4-yl)-N-(thiophen-2-ylmethyl)methanimine Lf) and three different silver(I) anions (nitrate, perchlorate and triflate). Structurally, the complexes adopted different coordination geometries, which included distorted linear or distorted tetrahedral geometry. The complexes were evaluated in vitro for their potential antibacterial and antioxidant activities. In addition, their interactions with calf thymus-DNA (CT-DNA) and bovine serum albumin (BSA) were evaluated. All the complexes had a wide spectrum of effective antibacterial activity against gram-positive and gram-negative bacterial and good antioxidant properties. The interactions of the complexes with CT-DNA and BSA were observed to occur either through intercalation or through a minor groove binder, while the interaction of the complexes with BSA reveals that some of the complexes can strongly quench the fluorescence of BSA through the static mechanism. The molecular docking studies of the complexes were also done to further elucidate the modes of interaction with CT-DNA and BSA.

Quinoline Functionalized Schiff Base Silver (I) Complexes: Interactions with Biomolecules and In Vitro Cytotoxicity, Antioxidant and Antimicrobial Activities.

A series of fifteen silver (I) quinoline complexes Q1-Q15 have been synthesized and studied for their biological activities. Q1-Q15 were synthesized from the reactions of quinolinyl Schiff base derivatives L1-L5 (obtained by condensing 2-quinolinecarboxaldehyde with various aniline derivatives) with AgNO3, AgClO4 and AgCF3SO3. Q1-Q15 were characterized by various spectroscopic techniques and the structures of [Ag(L1)2]NO3Q1, [Ag(L1)2]ClO4Q6, [Ag(L2)2]ClO4Q7, [Ag(L2)2]CF3SO3Q12 and [Ag(L4)2]CF3SO3Q14 were unequivocally determined by single crystal X-ray diffraction analysis. In vitro antimicrobial tests against Gram-positive and Gram-negative bacteria revealed the influence of structure and anion on the complexes' moderate to excellent antibacterial activity. In vitro antioxidant activities of the complexes showed their good radical scavenging activity in ferric reducing antioxidant power (FRAP). Complexes with the fluorine substituent or the thiophene or benzothiazole moieties are more potent with IC50 between 0.95 and 2.22 mg/mL than the standard used, ascorbic acid (2.68 mg/mL). The compounds showed a strong binding affinity with calf thymus-DNA via an intercalation mode and protein through a static quenching mechanism. Cytotoxicity activity was examined against three carcinoma cell lines (HELA, MDA-MB231, and SHSY5Y). [Ag(L2)2]ClO4Q7 with a benzothiazole moiety and [Ag(L4)2]ClO4Q9 with a methyl substituent had excellent cytotoxicity against HELA cells.